Cisplatin-induced ototoxicity in pediatric solid tumors: The role of glutathione S-transferases and megalin genetic polymorphisms
Cisplatin-induced ototoxicity, an important dose-limiting side effect, has proven high interindividual variability. Glutathione S-transferases (GSTs) are isoenzymes involved in cellular detoxification processes. Megalin has been demonstrated to bind aminoglycosides, known to be similar to cisplatin...
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th-cmuir.6653943832-528742018-09-04T09:33:50Z Cisplatin-induced ototoxicity in pediatric solid tumors: The role of glutathione S-transferases and megalin genetic polymorphisms Worawut Choeyprasert Rachchadol Sawangpanich Krisna Lertsukprasert Umaporn Udomsubpayakul Duantida Songdej Usanarat Unurathapan Samart Pakakasama Suradej Hongeng Medicine Cisplatin-induced ototoxicity, an important dose-limiting side effect, has proven high interindividual variability. Glutathione S-transferases (GSTs) are isoenzymes involved in cellular detoxification processes. Megalin has been demonstrated to bind aminoglycosides, known to be similar to cisplatin for their ototoxicity. The GSTs and megalin expression is genetically polymorphic, which might be responsible for the variability in cisplatin-induced ototoxicity. The genotyping of GSTM1, GSTT1 polymorphisms, and 2 nonsynonymous single nucleotide polymorphisms (SNPs) at megalin genes, rs2075252 and rs2228171, were performed in 68 children diagnosed with solid tumors who received cisplatin-based chemotherapy. After the end of treatment, audiometry demonstrated hearing loss in 79.4% of patients according to Brock classification. The cumulative cisplatin dose >400 mg/m2is associated with increased risk of cisplatin-induced ototoxicity [odds ratio (OR), 17.5; 95% confidence interval (CI), 3.09-98.62]. GSTT1 wild genotype and C-allele of rs2228171 SNPs of megalin gene occurred with higher frequency in patients with ototoxicity (P=0.023; OR, 10; 95% CI, 1.80-56.00 and P=0.034; OR, 2.67; 95% CI, 1.22- 5.82, respectively). In conclusion, our results suggested that GSTT1 wild genotype and C-allele of rs2228171 SNPs might be risk factors for ototoxicity. The cumulative cisplatin dose <400 mg/m2should be beneficial in order to ameliorate ototoxicity. Copyright © 2012 by Lippincott Williams & Wilkins. 2018-09-04T09:33:50Z 2018-09-04T09:33:50Z 2013-05-01 Journal 15363678 10774114 2-s2.0-84878653311 10.1097/MPH.0b013e3182707fc5 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84878653311&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/52874 |
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Medicine Worawut Choeyprasert Rachchadol Sawangpanich Krisna Lertsukprasert Umaporn Udomsubpayakul Duantida Songdej Usanarat Unurathapan Samart Pakakasama Suradej Hongeng Cisplatin-induced ototoxicity in pediatric solid tumors: The role of glutathione S-transferases and megalin genetic polymorphisms |
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Cisplatin-induced ototoxicity, an important dose-limiting side effect, has proven high interindividual variability. Glutathione S-transferases (GSTs) are isoenzymes involved in cellular detoxification processes. Megalin has been demonstrated to bind aminoglycosides, known to be similar to cisplatin for their ototoxicity. The GSTs and megalin expression is genetically polymorphic, which might be responsible for the variability in cisplatin-induced ototoxicity. The genotyping of GSTM1, GSTT1 polymorphisms, and 2 nonsynonymous single nucleotide polymorphisms (SNPs) at megalin genes, rs2075252 and rs2228171, were performed in 68 children diagnosed with solid tumors who received cisplatin-based chemotherapy. After the end of treatment, audiometry demonstrated hearing loss in 79.4% of patients according to Brock classification. The cumulative cisplatin dose >400 mg/m2is associated with increased risk of cisplatin-induced ototoxicity [odds ratio (OR), 17.5; 95% confidence interval (CI), 3.09-98.62]. GSTT1 wild genotype and C-allele of rs2228171 SNPs of megalin gene occurred with higher frequency in patients with ototoxicity (P=0.023; OR, 10; 95% CI, 1.80-56.00 and P=0.034; OR, 2.67; 95% CI, 1.22- 5.82, respectively). In conclusion, our results suggested that GSTT1 wild genotype and C-allele of rs2228171 SNPs might be risk factors for ototoxicity. The cumulative cisplatin dose <400 mg/m2should be beneficial in order to ameliorate ototoxicity. Copyright © 2012 by Lippincott Williams & Wilkins. |
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Journal |
author |
Worawut Choeyprasert Rachchadol Sawangpanich Krisna Lertsukprasert Umaporn Udomsubpayakul Duantida Songdej Usanarat Unurathapan Samart Pakakasama Suradej Hongeng |
author_facet |
Worawut Choeyprasert Rachchadol Sawangpanich Krisna Lertsukprasert Umaporn Udomsubpayakul Duantida Songdej Usanarat Unurathapan Samart Pakakasama Suradej Hongeng |
author_sort |
Worawut Choeyprasert |
title |
Cisplatin-induced ototoxicity in pediatric solid tumors: The role of glutathione S-transferases and megalin genetic polymorphisms |
title_short |
Cisplatin-induced ototoxicity in pediatric solid tumors: The role of glutathione S-transferases and megalin genetic polymorphisms |
title_full |
Cisplatin-induced ototoxicity in pediatric solid tumors: The role of glutathione S-transferases and megalin genetic polymorphisms |
title_fullStr |
Cisplatin-induced ototoxicity in pediatric solid tumors: The role of glutathione S-transferases and megalin genetic polymorphisms |
title_full_unstemmed |
Cisplatin-induced ototoxicity in pediatric solid tumors: The role of glutathione S-transferases and megalin genetic polymorphisms |
title_sort |
cisplatin-induced ototoxicity in pediatric solid tumors: the role of glutathione s-transferases and megalin genetic polymorphisms |
publishDate |
2018 |
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https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84878653311&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/52874 |
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